Introduction
An excessive perioperative inflammatory reaction can lead to more postoperative complications in patients treated for gastrointestinal cancers. It has been suggested that this ...inflammatory reaction leads to oxidative stress. The most important nonenzymatic antioxidants are serum free thiols. The purpose of this study was to evaluate whether high preoperative serum free thiol levels are associated with short-term clinical outcomes.
Methods
Blood samples were drawn before, at the end of, and 1 and 2 days after surgery of a consecutive series of patients with gastrointestinal cancer. Serum free thiols were detected using a colorimetric detection method using Ellman’s reagent. Short-term clinical outcomes were defined as 30-day complications (Clavien-Dindo ≥2) and length of hospital stay. Logistic regression was applied to examine the association between serum free thiol levels and short-term patient outcomes.
Results
Eighty-one patients surgically treated for gastrointestinal cancer were included in the study. Median age was 68 (range 26–87) years, and 28% were female. Patients in the lowest tertile of preoperative serum free thiols had a threefold higher risk to develop postoperative complications (odds ratio OR: 3.4; 95% confidence interval CI:1.1–10.7) and a fourfold higher risk to have an increased length of stay in the hospital (OR 4.0; 95% CI 1.3–12.9) compared with patients in the highest tertile.
Conclusions
Patients with lower preoperative serum free thiol levels, indicating a decrease in extracellular antioxidant capacity and therefore an increase in systemic oxidative stress, are more likely to develop postoperative complications and show a longer in hospital stay than patients with higher serum free thiol levels.
Thermal evaporation is the current standard for the manufacture of small molecule organic light emitting diodes (smOLEDs), but it requires vacuum process, complicated shadow masks and is inefficient ...in material utilization, resulting in high cost of ownership. As an alternative, wet solution deposition can provide significant cost savings by enabling high-volume, large-area electronics on flexible substrates at low fabrication costs. In this report we present inkjet printing as a method to produce three active layers in a smOLED stack: a hole-injection layer, a hole transport layer and an emissive layer. The OLED lighting application sets high demands to a uniform light output over an area. This requires homogeneous deposition of the electro-active layers and this poses a significant challenge. OLED device efficiency is greatly influenced by the printed layer morphology and the quality of the deposited layers. Therefore inkjet processed smOLED device efficiency will be compared with reference devices made via vacuum deposition.
► Inkjet printing of small molecules to produce organic light emitting diodes is done. ► Printed layer thickness can be controlled in a reproducible way. ► Working devices with inkjet printed layers can be made having normal efficiency. ► It is difficult to control recrystallization in multi-layer systems.
In combination with microspotting, whole-blood microfluidics can provide high-throughput information on multiple platelet functions in thrombus formation. Based on assessment of the inter- and ...intra-subject variability in parameters of microspot-based thrombus formation, we aimed to determine the platelet factors contributing to this variation. Blood samples from 94 genotyped healthy subjects were analyzed for conventional platelet phenotyping: i.e. hematologic parameters, platelet glycoprotein (GP) expression levels and activation markers (24 parameters). Furthermore, platelets were activated by ADP, CRP-XL or TRAP. Parallel samples were investigated for whole-blood thrombus formation (6 microspots, providing 48 parameters of adhesion, aggregation and activation). Microspots triggered platelet activation through GP Ib-V-IX, GPVI, CLEC-2 and integrins. For most thrombus parameters, inter-subject variation was 2-4 times higher than the intra-subject variation. Principal component analyses indicated coherence between the majority of parameters for the GPVI-dependent microspots, partly linked to hematologic parameters, and glycoprotein expression levels. Prediction models identified parameters per microspot that were linked to variation in agonist-induced α
β
activation and secretion. Common sequence variation of
and
, associated with GPVI-induced α
β
activation and secretion, affected parameters of GPVI-and CLEC-2-dependent thrombus formation. Subsequent analysis of blood samples from patients with Glanzmann thrombasthenia or storage pool disease revealed thrombus signatures of aggregation-dependent parameters that were subject-dependent, but not linked to GPVI activity. Taken together, this high-throughput elucidation of thrombus formation revealed patterns of inter-subject differences in platelet function, which were partly related to GPVI-induced activation and common genetic variance linked to GPVI, but also included a distinct platelet aggregation component.
Atherothrombosis is a major cause of cardiovascular events. However, animal models to study this process are scarce.
We describe the first murine model of acute thrombus formation upon plaque rupture ...to study atherothrombosis by intravital fluorescence microscopy.
Localized rupture of an atherosclerotic plaque in a carotid artery from Apoe(-/-) mice was induced in vivo using ultrasound. Rupture of the plaque and formation of localized thrombi were verified by two-photon laser scanning microscopy (TPLSM) in isolated arteries, and by immunohistochemistry. The thrombotic reaction was quantified by intravital fluorescence microscopy.
Inspection of the ultrasound-treated plaques by histochemistry and TPLSM demonstrated local damage, collagen exposure, luminal thrombus formation as well as intra-plaque intrusion of erythrocytes and fibrin. Ultrasound treatment of healthy carotid arteries resulted in endothelial damage and limited platelet adhesion. Real-time intravital fluorescence microscopy demonstrated rapid platelet deposition on plaques and formation of a single thrombus that remained subocclusive. The thrombotic process was antagonized by thrombin inhibition, or by blocking of collagen or adenosine diphosphate receptor pathways. Multiple thrombi were formed in 70% of mice lacking CD40L.
Targeted rupture of murine plaques results in collagen exposure and non-occlusive thrombus formation. The thrombotic process relies on platelet activation as well as on thrombin generation and coagulation, and is sensitive to established and novel antithrombotic medication. This model provides new possibilities to study atherothrombosis in vivo.
Resistance to triazoles was recently reported in Aspergillus fumigatus isolates cultured from patients with invasive aspergillosis. The prevalence of azole resistance in A. fumigatus is unknown. We ...investigated the prevalence and spread of azole resistance using our culture collection that contained A. fumigatus isolates collected between 1994 and 2007.
We investigated the prevalence of itraconazole (ITZ) resistance in 1,912 clinical A. fumigatus isolates collected from 1,219 patients in our University Medical Centre over a 14-y period. The spread of resistance was investigated by analyzing 147 A. fumigatus isolates from 101 patients, from 28 other medical centres in The Netherlands and 317 isolates from six other countries. The isolates were characterized using phenotypic and molecular methods. The electronic patient files were used to determine the underlying conditions of the patients and the presence of invasive aspergillosis. ITZ-resistant isolates were found in 32 of 1,219 patients. All cases were observed after 1999 with an annual prevalence of 1.7% to 6%. The ITZ-resistant isolates also showed elevated minimum inhibitory concentrations of voriconazole, ravuconazole, and posaconazole. A substitution of leucine 98 for histidine in the cyp51A gene, together with two copies of a 34-bp sequence in tandem in the gene promoter (TR/L98H), was found to be the dominant resistance mechanism. Microsatellite analysis indicated that the ITZ-resistant isolates were genetically distinct but clustered. The ITZ-sensitive isolates were not more likely to be responsible for invasive aspergillosis than the ITZ-resistant isolates. ITZ resistance was found in isolates from 13 patients (12.8%) from nine other medical centres in The Netherlands, of which 69% harboured the TR/L98H substitution, and in six isolates originating from four other countries.
Azole resistance has emerged in A. fumigatus and might be more prevalent than currently acknowledged. The presence of a dominant resistance mechanism in clinical isolates suggests that isolates with this mechanism are spreading in our environment.
Phenotypic heterogeneity and incomplete penetrance are common in patients with hypertrophic cardiomyopathy (HCM). We aim to improve the understanding in genotype-phenotype correlations in HCM, ...particularly the contribution of an MYL2 founder mutation and risk factors to left ventricular hypertrophic remodelling.
We analysed 14 HCM families of whom 38 family members share the MYL2 c.64G > A p.(Glu22Lys) mutation and a common founder haplotype. In this unique cohort, we investigated factors influencing phenotypic outcome in addition to the primary mutation. The mutation alone showed benign disease manifestation with low penetrance. The co-presence of additional risk factors for hypertrophy such as hypertension, obesity, or other sarcomeric gene mutation increased disease penetrance substantially and caused HCM in 89% of MYL2 mutation carriers (P = 0.0005). The most prominent risk factor was hypertension, observed in 71% of mutation carriers with HCM and an additional risk factor.
The MYL2 mutation c.64G > A on its own is incapable of triggering clinical HCM in most carriers. However, the presence of an additional risk factor for hypertrophy, particularly hypertension, adds to the development of HCM. Early diagnosis of risk factors is important for early treatment of MYL2 mutation carriers and close monitoring should be guaranteed in this case. Our findings also suggest that the presence of hypertension or another risk factor for hypertrophy should not be an exclusion criterion for genetic studies.
Refractive errors are the most common ocular disorders worldwide and may lead to blindness. Although this trait is highly heritable, identification of susceptibility genes has been challenging. We ...conducted a genome-wide association study for refractive error in 5,328 individuals from a Dutch population-based study with replication in four independent cohorts (combined 10,280 individuals in the replication stage). We identified a significant association at chromosome 15q14 (rs634990, P = 2.21 × 10−14). The odds ratio of myopia compared to hyperopia for the minor allele (minor allele frequency = 0.47) was 1.41 (95% CI 1.16-1.70) for individuals heterozygous for the allele and 1.83 (95% CI 1.42-2.36) for individuals homozygous for the allele. The associated locus is near two genes that are expressed in the retina, GJD2 and ACTC1, and appears to harbor regulatory elements which may influence transcription of these genes. Our data suggest that common variants at 15q14 influence susceptibility for refractive errors in the general population.
Summary
Background
Treatment goals have been developed to optimize daily clinical practice psoriasis care, but have not yet been studied in real life.
Objectives
To investigate to what extent ...treatment decisions made by dermatologists in daily clinical practice for patients with psoriasis on biologics are already in accordance with treatment goals without the active application of the treatment goals algorithm.
Methods
Data were extracted from a prospective daily practice cohort of patients with psoriasis on biologics. Analysis was done on effectiveness (Psoriasis Area and Severity Index score) and quality of life (Dermatology Life Quality Index questionnaire). Treatment decisions such as dosage adjustments, combination treatments, or switching therapy were compared with the treatment goals algorithm.
Results
In 64% (253 of 395) of visits, physicians followed the treatment goals algorithm. There were 162 (41%) visits in which there should have been a treatment modification according to treatment goals (group Modify) and a modification was indeed made in 59 of these 162 visits (36%). In 233 (59%) visits no treatment modification was necessary (group Continue) and therapy was indeed not modified in 194 of 233 visits (83%).
Conclusions
Physicians acted in accordance with treatment goals in the majority of patient visits. In the patient group not achieving these goals, physicians should have modified therapy according to treatment goals but continued the same therapeutic regimen in the majority of visits. Optimizing therapy and defining barriers in the latter group might increase treatment results in daily practice psoriasis care.
What's already known about this topic?
A European consensus on treatment goals was established in 2011 to guide physicians in the treatment of psoriasis.
These treatment goals have been evaluated for adalimumab therapy using data from three randomized clinical trials.
What does this study add?
Treatment decisions made by dermatologists for patients with psoriasis on biologics in daily clinical practice are already in accordance with the treatment goals from before application of the European consensus.
This study provides a starting point from which to evaluate the influence of the actual implementation of treatment goals in daily practice.
Summary
Background
Although the effectiveness of biologics for psoriasis has been measured extensively with objective outcome measures, studies based on subjective, patient‐reported outcome measures ...remain scarce.
Objectives
To investigate satisfaction with medication, as measured by the Treatment Satisfaction Questionnaire for Medication (TSQM) for biologics in daily practice psoriasis care in the first 6 months of treatment; and to identify possible differences in satisfaction with medication between patients experienced (biologics‐experienced) and inexperienced (biologics‐inexperienced) in the use of biologics.
Methods
TSQM baseline measurements were compared using measurements taken after 6 months, using the Wilcoxon signed‐rank test for paired comparisons. Intention‐to‐treat with last observation carried forward (ITT with LOCF) and as‐treated analyses were performed. The difference between biologics‐experienced and biologics‐inexperienced patients for TSQM was analysed using ITT with LOCF. At 6 months, outcomes for biologics‐experienced and biologics‐inexperienced patients were compared using the Mann–Whitney U‐test.
Results
One hundred and six patients were eligible for analysis, and treated with etanercept (n = 34), adalimumab (n = 49) or ustekinumab (n = 23). Fifty‐four per cent of patients were biologics‐inexperienced. A statistically significant improvement was seen in all domains of the TSQM (‘effectiveness’, ‘side‐effects’, ‘convenience’ and ‘global satisfaction’) by comparison of months 3 or 6 with baseline (all P ≤ 0·02). After 6 months, biologics‐inexperienced patients scored better on the ‘global satisfaction’ domain than biologics‐experienced patients (P < 0·01).
Conclusions
We provide a prospective, longitudinal analysis of TSQM for biologics in daily practice psoriasis care. High satisfaction rates were achieved. The ‘effectiveness’ and ‘convenience’ domains showed the most room for improvement.
What's already known about this topic?
Maximum satisfaction with medication is thought to be positively related to adherence, health‐related quality of life and patients' preferences.
As shown in cross‐sectional research, patients' dissatisfaction with treatment plays an important role in psoriasis. Those receiving biologics are the most satisfied with treatment among patients with psoriasis.
In an open‐label extension trial with etanercept, significant improvement in the ‘global satisfaction’, ‘effectiveness’ and ‘convenience’ domains was achieved after 3 months of treatment.
What does this study add?
A prospective, longitudinal study on satisfaction with etanercept, adalimumab and ustekinumab for patients with psoriasis in daily practice.
Significantly improved satisfaction rates (using the Treatment Satisfaction Questionnaire for Medication) were achieved after 3 and 6 months. As reported by the patients, the ‘effectiveness’ and ‘convenience’ domains showed the most room for improvement.
After 6 months, biologics‐inexperienced patients scored significantly better on the ‘global satisfaction’ domain than experienced patients.
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